The long term objectives are to understand the physiological and pathophysiological roles of gastrin in the regulation of gastric acid secretion, to understand the nature and significance of interactions between gastrin and other hormonal and paracrine regulatory peptides that influence parietal cell function, and to understand the regulation of synthesis and secretion of gastrin by gastrin cells. The physiological role of circulating gastrin will be studied by specific immunoneutralization of gastrin by monoclonal antibodies. The potential endocrine and paracrine roles of somatostatin as a peripheral antagonist of gastrin action and of gastrin release will be studied by specific immunoneutralization with IgG and Fab fragments of monoclonal antibodies to somatostatin. Biosynthesis and processing of gastrin will be studied by use of antibodies specific for different regions of the progastrin molecule and by measurement of gastrin mRNA. Release of gastrin by apical and basal lateral stimulants will be studied in an isolated canine gastrin cell preparation. The intracellular mediators of the gastrin response to phenylalanine will be defined. Finally, parallel and nonparallel regulation of gastrin cell proliferation, gastrin synthesis, gastrin processing, and gastrin release will be studied in rats and dogs.